Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids

Abstract

treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids. J Appl Physiol 98: [981][982][983][984][985][986][987][988][989][990] 2005. First published November 12, 2004; doi:10.1152/japplphysiol.01029.2004.-Dexamethasone is used as treatment for a variety of neonatal syndromes, including respiratory distress. The present study utilized the power of comprehensive lipid profiling to characterize changes in lipid metabolism in the neonatal lung and brain associated with dexamethasone treatment and also determined the interaction of dexamethasone with hypoxia. A 4-day tapering-dose regimen of dexamethasone was administered at 0800 on postnatal days 3 (0.5 mg/kg), 4 (0.25 mg/kg), 5 (0.125 mg/kg), and 6 (0.05 mg/kg). A subgroup of rats was exposed to hypoxia from birth to 7 days of age. Dexamethasone treatment elicited numerous specific changes in the lipid profile of the normoxic lung, such as increased concentrations of saturated fatty acids in the phosphatidylcholine and cholesterol ester classes. These increases were more profound in the lungs of hypoxic pups. Additional increases in cardiolipin concentrations were also measured in lungs of hypoxic pups treated with dexamethasone. We measured widespread increases in serum lipids after dexamethasone treatment, but the effects were not equivalent between normoxic and hypoxic pups. Dexamethasone treatment in hypoxic pups increased 20:4n6 and 22:6n3 concentrations in the free fatty acid class of the brain. Our results suggest that dexamethasone treatment in neonates elicits specific changes in lung lipid metabolism associated with surfactant production, independent of changes in serum lipids. These findings illustrate the benefits of dexamethasone on lung function but also raise the potential for negative effects due to hyperlipidemia and subtle changes in brain lipid metabolism. hypoxia; glucocorticoid therapy; neonate INHALED AND SYSTEMIC GLUCOCORTICOIDS have been widely used to treat syndromes of perinatal distress, many of which have an inflammatory component requiring pharmacological therapy (3,7,23,25,53). Dexamethasone, a highly potent glucocorticoid, has been the treatment of choice for neonates who are hypoxic due to cardiopulmonary conditions such as bronchopulmonary dysplasia (2,13,33,46,50). A major motivation for this therapy is the promotion of surfactant production and lung maturation and to induce closure of the ductus arteriosus (6,34,43,45,47). Dexamethasone decreases the duration of ventilatory support and lowers the incidence of chronic lung disease (13,23,33,50).Dexamethasone therapy, however, may lead to unfavorable long-term sequelae, including decreases in neuromotor and cognitive function (4,15,30,36,37,55), and may also lead to left ventricular abnormalities and metabolic dysfunction (5,14,17,24). A report of lipid intolerance in infants treated with dexamethasone highlights this potential for long-term metabolic dysfunction (2). It is for these reasons that the use of dexamethasone in neonates is decreasing (39) and...

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

“…We have also demonstrated that ghrelin, a hormone released by the GI tract that has a wide variety of endocrine and metabolic actions, is increased by dexamethasone therapy ( 15 ). The differential actions of leptin and ghrelin on food intake, insulin sensitivity, and metabolic function made it clear that these two factors per se could not account for the changes in growth hormone ( 7 ), IGF-I ( 8 ), body composition ( 7,8 ), weight gain ( 7,8 ), lipid profiles ( 12,14 ), and other parameters of metabolic function in our previous studies.…”

“…Furthermore, we have recently demonstrated that a tapering regimen of the glucocorticoid dexamethasone, administered to mimic clinical practice ( 11 ), results in hyperinsulinemia with normoglycemia and decreased weight gain ( 12 ). There is also a significant interaction between dexamethasone, which is often used to treat neonatal cardiopulmonary disorders ( 13 ), and hypoxia with respect to many parameters of metabolic function ( 12,14,15 ).…”

Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation

“…The dexamethasone exerts a series of effects on injured neural tissue (13,20). These effects are the regulation of energy metabolism, the prevention of progressive posttraumatic ischemia, the prevention of neurofilament degradation and the inhibition of membrane lipid hydrolysis (3,4,25). Thus, it has been long believed that, with dexamethasone treatment, the structural and functional integrity of biological membranes can be preserved (3,15).…”

“…These effects are the regulation of energy metabolism, the prevention of progressive posttraumatic ischemia, the prevention of neurofilament degradation and the inhibition of membrane lipid hydrolysis (3,4,25). Thus, it has been long believed that, with dexamethasone treatment, the structural and functional integrity of biological membranes can be preserved (3,15). The primary mechanism of the neuroprotective effect of dexamethasone is the inhibition of lipid peroxidation (4,5,15).…”

“…Whole fetal rat brains were removed at the end of the reperfusion period for tissue sampling. A very small portion of the brain tissue (≈1mm 3 ) from left motor cortex was preserved in glutaraldehyde for the electron microscopic analysis. The rest of the whole brains were stored in liquid nitrogen (-196 0 C) for lipid peroxidation.…”